Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.

Details

Serval ID
serval:BIB_9F01A797619F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.
Journal
Antimicrobial agents and chemotherapy
Author(s)
Perrottet N., Csajka C., Pascual M., Manuel O., Lamoth F., Meylan P., Aubert J.D., Venetz J.P., Soccal P., Decosterd L.A., Biollaz J., Buclin T.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
07/2009
Peer-reviewed
Oui
Volume
53
Number
7
Pages
3017-3023
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.
Keywords
Administration, Oral, Adolescent, Adult, Aged, Antiviral Agents/pharmacokinetics, Female, Ganciclovir/analogs & derivatives, Ganciclovir/pharmacokinetics, Glomerular Filtration Rate, Humans, Male, Middle Aged, Organ Transplantation, Valganciclovir, Viremia/drug therapy, Viremia/prevention & control, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
04/10/2019 7:03
Last modification date
05/10/2019 5:26
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